In the last decade, inhibitors targeting immune checkpoint molecules such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed cell death-ligand 1 (PD-L1) brought about a major paradigm shift in cancer treatment. These immune checkpoint inhibitors (ICIs) improved the overall survival of a variety of cancer such as malignant melanoma and non-small lung cancer. In addition, numerous clinical trials for additional indication of ICIs including adjuvant and neo-adjuvant therapies are also currently ongoing. Therefore, more and more patients will receive ICIs in the future. However, despite the improved outcome of the cancer treatment by ICIs, the efficacy remains still limited and tumor regression have not been obtained in many cancer patients. In addition, treatment with ICIs is also associated with substantial toxicities, described as immune-related adverse events (irAEs). Therefore, biomarkers to predict tumor response and occurrence of irAEs by the treatment with ICIs are required to avoid overtreatment of ICIs and minimize irAEs development. Whereas, numerous factors have been reported as potential biomarkers for tumor response to ICIs, factors for predicting irAE have been less reported. In this review, we show recent advances in the understanding of biomarkers for tumor response and occurrence of irAEs in cancer patients treated with ICIs.

Extramammary Paget’s disease (EMPD) is a rare neoplasm that usually develops in apocrine gland-bearing areas, such as the vulva, scrotum, and penis. EMPD may present with a focal, multifocal, or an ectopic lesion. Clinically, EMPD lesions often exhibit infiltrative erythema, which is sometimes similar to other skin disorders such as eczema. While primary EMPD arises as intraepithelial neoplasm of the epidermis, EMPD-like lesions may occur from epidermotropic spread of malignant cells or direct extension from an underlying internal neoplasm, known as secondary EMPD. Because treatment strategies differ for primary EMPD and secondary EMPD, accurate diagnosis based on detailed histopathological evaluation is required. In the early stages, EMPD usually shows indolent growth, and most cases are diagnosed as carcinoma in situ. However, invasive lesions may result in metastases, and deep invasion is associated with high incidence of metastases. Conventional chemotherapies have been used for EMPD treatment in patients with distant metastases, but the efficacy is not satisfactory, and the prognosis for such patients remains poor. Recent studies have provided various insights into the molecular pathogenesis of the development and advancement of EMPD, which may lead to novel treatment approaches for metastatic EMPD. This review addresses the diagnosis, pathogenesis, and treatment of EMPD with focus on recent progress in understanding this disease.